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Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden
Drzezga A, Becker JA, Van Dijk KR, Sreenivasan A, Talukdar T, Sullivan C, Schultz AP, Sepulcre J et al.. Brain : a journal of neurology, 2011-04-13
Topic: Amyloid, tau and blood-test diagnosis
Disruption of functional connectivity between brain regions may represent an early functional consequence of β-amyloid pathology prior to clinical Alzheimer's disease. We aimed to investigate if non-demented older individuals with increased amyloid burden demonstrate disruptions of functional whole-brain connectivity in cortical hubs (brain regions typically highly connected to multiple other brain areas) and if these disruptions are associated with neuronal dysfunction as measured with fluorodeoxyglucose-positron emission tomography. In healthy subjects without cognitive symptoms and patients with mild cognitive impairment, we used positron emission tomography to assess amyloid burden and cerebral glucose metabolism, structural magnetic resonance imaging to quantify atrophy and novel resting state functional magnetic resonance imaging processing methods to calculate whole-brain connectivity. Significant disruptions of whole-brain connectivity were found in amyloid-positive patients with mild cognitive impairment in typical cortical hubs (posterior cingulate cortex/precuneus), strongly overlapping with regional hypometabolism. Subtle connectivity disruptions and hypometabolism were already present in amyloid-positive asymptomatic subjects. Voxel-based morphometry measures indicate that these findings were not solely a consequence of regional atrophy. Whole-brain connectivity values and metabolism showed a positive correlation with each other and a negative correlation with amyloid burden. These results indicate that disruption of functional connectivity and hypometabolism may represent early functional consequences of emerging molecular Alzheimer's disease pathology, evolving prior to clinical onset of dementia. The spatial overlap between hypometabolism and disruption of connectivity in cortical hubs points to a particular susceptibility of these regions to early Alzheimer's-type neurodegeneration and may reflect a link between synaptic dysfunction and functional disconnection.
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APA 7th
Drzezga, A., Becker, J. A., Van Dijk, K. R., Sreenivasan, A., Talukdar, T., Sullivan, C., et al. (2011). Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden. Brain : a journal of neurology. https://doi.org/10.1093/brain/awr066
Vancouver
Drzezga A, Becker JA, Van Dijk KR, Sreenivasan A, Talukdar T, Sullivan C, et al. Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden. Brain : a journal of neurology. 2011. doi:10.1093/brain/awr066. PMID: 21490054.
BibTeX
@article{drzezga2011-21490054,
author = {Drzezga, A. and Becker, J. A. and Van Dijk, K. R. and Sreenivasan, A. and Talukdar, T. and Sullivan, C. and Schultz, A. P. and Sepulcre, J. and others},
title = {{Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden}},
journal = {Brain : a journal of neurology},
year = {2011},
doi = {10.1093/brain/awr066},
pmid = {21490054},
url = {https://doi.org/10.1093/brain/awr066}
}
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Key findings
- We aimed to investigate if non-demented older individuals with increased amyloid burden demonstrate disruptions of functional whole-brain connectivity in cortical hubs (brain regions typically highly connected to multiple other brain areas) and if these disruptions are associated with neuronal dysfunction as measured with fluorodeoxyglucose-positron emission tomography.
- Significant disruptions of whole-brain connectivity were found in amyloid-positive patients with mild cognitive impairment in typical cortical hubs (posterior cingulate cortex/precuneus), strongly overlapping with regional hypometabolism.
- Voxel-based morphometry measures indicate that these findings were not solely a consequence of regional atrophy.
- These results indicate that disruption of functional connectivity and hypometabolism may represent early functional consequences of emerging molecular Alzheimer's disease pathology, evolving prior to clinical onset of dementia.
Why it matters
This imaging study found that non-demented people with elevated amyloid had disrupted connectivity in highly connected brain regions, along with reduced metabolism, and that subtle changes were already present in those without symptoms. The authors note these findings were not solely explained by regional atrophy.
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Study details
- Evidence strengthLow
How this study scored 57/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 380 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.4 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 4 / 6 | Cited 17.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 21 other studies in this library |
| Still being cited | 2 / 4 | Cited 49 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Reisa Anne Sperling: h-index 157 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21490054) |
| Free to read | 2 / 2 | Free to read |
| Total | 57 / 100 | — |
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